For the development of today's medicine, the discovery and application of an antibiotic(s) have been important. However, in recent years, problems with side effects of antibiotics and the emergence of multi-drug-resistant microbes due to mutation have been much discussed. The idea of a ‘probiotic(s)’ as opposed to an ‘antibiotic(s)’ has recently been widely recognized in society. A probiotic(s) means ‘a useful microorganism that improves the bacterial flora in the gastrointestinal tract and can bring a beneficial effect to a host, and a growth-promoting substance therefor’, and the idea has been born of such a probiotic(s) being used so as to act on the flora (bacterial flora) in the gastrointestinal tract (intraoral or enteric) and preventing or improving a disease while making the flora healthier.
The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the bHLH-PAS family, appears to be expressed in most cells and tissue, and is known to activate the transcription of various genes by ligand binding. As a ligand for the AhR, a compound such as a dioxin or a polychlorinated biphenyl is known, but an endogenous ligand for the receptor is unknown.
The AhR in a state in which it is not bound to a ligand is inactive, and is present within cytoplasm being associated with a molecular chaperone such as Hsp90. When inactive AhR binds to a ligand, the molecular chaperone dissociates, and the activated AhR translocates into the nucleus. The AhR that has translocated into the nucleus is associated with a molecule called the ARNT (AhR Nucleus Translocator) to form a heterodimer, and interacts with an enhancer sequence called a xenobiotic responsive element (XRE) on DNA to thus activate the transcription of a downstream gene.
In recent years, it has been found that production of prostaglandin E2 (PGE2) is promoted by activation of an AhR pathway (Non-Patent Document 1) and that PGE2 is involved in protection against gastrointestinal damage (Non-Patent Document 2). Trials have therefore been started to see whether protection from gastrointestinal damage is possible by promoting the production of PGE2 by AhR activation.
As one of the trials, it has been reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is known as an AhR ligand, suppresses the inflammatory response of ulcerative colitis induced by dextran sodium sulfate (DSS) (Non-Patent Document 3). This report discloses that in a DSS-treated mouse to which TCDD had been administered, compared with one to which TCDD had not been administered, weight loss, shortening of the intestinal tract, inflammation score, and the production of inflammatory cytokines were significantly suppressed.